The YCCC requests continued support for grant related activities that include 9 shared resources, 14 established research programs, 1 developing program and a new clinical trials protocol review and development system. These programs are managed under the direction of four associate directors, working in conjunction with the Director, and an Associate Director, and his administrative staff in four areas: Basic Science, Clinical Science, and Cancer Prevention Research, and Community Research. An Associate Director of Education oversees the Education and training programs of the center. We request continued support for this senior leadership and leaders of established research programs, for planning and evaluation, and developmental funds, and administration. Interdisciplinary coordination in the clinical areas is facilitated by the use of disease oriented units in Breast, GU, GI and Head and Neck cancers; Melanoma, Lymphomas, Brain tumor and a support unit on bone marrow transplantation. Yale's extraordinary depth in Molecular Biology provides focus for the centers translational research. The clinical Research programs are organized around major specialties and have been augmented in this grant cycle by an expanded emphasis on the use of new technology to overcome the major limitations of cancer treatment and prevention by transferring through the means of a shared resource, formerly the tissue retrieval resource, and now the Critical technologies Shared Resource, the capability to include sophisticated molecular technologies in clinical trials in diagnosis, treatment and Prevention, to allow the proper preservation of tissue, and the measurement of both structure and function to correlate with outcome. A new shared resource since the last grant cycle, Clinical Pharmacology, takes advantage of the YCCC's strength in Cancer Pharmacology. Other shared resources include, Flow Cytometry, Animal Tumor Models, Tissue Culture/Media Preparation, Mass Spectrometry, a Cesium-13T Irradiator, and a Transgenic Mouse Shared Resource. The basic research programs in Pathology, Molecular Oncology and Development, Molecular Virology and Cell Biology all emphasize research on oncogenes and suppressor oncogenes vis-a-vis the cell signaling systems. The Program in Immunology focuses on regulation of antigen and growth control processing by T-cells. The Developmental Therapeutics?Chemotherapy Program aims at developing anticancer agents directed at newly identified molecular targets. A developing program in Cancer Genetics will attempt to translate these activities into clinically useful tools.